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Clinical Pharmacy and Pharmacology

Paris, France
 

Reduced LDL-cholesterol levels in patients with coronary artery disease are paralleled by improved endothelial function: An observational study in patients from 2003 and 2007

Author(s): Delles C, Dymott JA, Neisius U, Rocchiccioli JP, Bryce GJ, et al.

Abstract

Objective: Recent guidelines recommend more aggressive lipid-lowering in secondary prevention protocols. We examined whether this resulted in improved endothelial function.

Methods: We studied saphenous vein specimens of patients undergoing surgical coronary revascularisation in 2007 and compared results with those of patients examined in 2003. Endothelium-dependent vasodilation was assessed by relaxation to calcium ionophore A23187, and vascular superoxide production by lucigenin enhanced chemiluminescence.

Results: Statin dose increased from 26+/-16 mg/d in 2003 to 37+/-17 mg/d in 2007 (P<0.001), and total (4.0+/-0.9 mmol/L vs 4.8+/-1.0 mmol/L) and LDL-cholesterol levels (2.0+/-0.7 mmol/L vs 3.0+/-0.9 mmol/L) were lower in 2007 compared to 2003 (P<0.001; n=90 each). Endothelium-dependent vasodilation was greater in 2007 (44+/-15%) compared to 2003 (28+/-12%; n=36 each; P<0.001). Vascular superoxide derived from endothelial NO synthase (eNOS) was lower in 2007 than in 2003 (reduction by NG-nitro-L-arginine-methyl ester, 0.29+/-0.21 nmol/(mg min) vs 0.09+/-0.20 nmol/(mg min); P=0.002). In linear regression analysis, LDL-cholesterol levels have been shown to be the major determinant of endothelial function in the combined 2003 and 2007 cohort.

Conclusion: Intensive lipid-lowering is associated with improved endothelial function and reduced superoxide production from eNOS. Further improvement in vascular function could be achieved by targeting other sources of superoxide including xanthine oxidase.

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